1. Field of the Invention
The present invention is directed to methods and compositions that combine nutritional, health and/or medical benefits provided to mammals by edible oils, particularly by omega-3 fatty acids, with nutritional, health and/or medical benefits provided to mammals by vitamins and/or minerals, particularly by B vitamins.
The present invention relates to compositions for an oral administration to mammals in an oral dosage form, or in a form of a suppository, comprising one or more edible oils, one or more water-soluble vitamins and/or minerals, one or more edible suspending agents that include phytosterols, phytosterol esters, plant stanols or plant stanol esters, or a combination thereof, and, optionally, one or more other components, such as antioxidants, emulsifiers, diluents and/or oil-soluble vitamins and/or minerals. The one or more edible oils preferably include one or more omega-3 fatty acids, and are uniformly combined. The one or more vitamins and/or minerals preferably include one or more water-soluble and oil-insoluble B vitamins, and more preferably include vitamin B6 (pyridoxine), vitamin B9 (folic acid or folate) and/or vitamin B12 (cyanocobalamin, cobalamin, cobalamin bound to recombinant intrinsic factor (rhIF) and/or reduced forms of cobalamin), which may be present in any combination. The one or more vitamins and/or minerals preferably are present in a solid state, and in the form of a uniform mixture, and are uniformly suspended within the one or more edible oils, or are present in an aqueous solution that is a continuous or disperse phase of an emulsion including the one or more edible oils. The one or more edible suspending agents preferably include a combination of CardioAid™-M phytosterols and CardioAid™-S phytosterol esters.
The present invention also relates to methods for producing such compositions, and to methods for using such compositions to provide one or more nutritional, health and/or medical benefits to a mammal, or to enhance one or more of such benefits in a mammal.
Examples of water-soluble vitamins that may be present in the compositions of the invention include the B-vitamins, and more particularly, at least one of vitamin B6, vitamin B9, and vitamin B12, or any combination thereof. The water-soluble vitamins and/or minerals are, optionally, present in a solid-state form such as an amorphous powder or a milled material, for example, a finely milled crystalline material, but can also be present in an aqueous or other solution that is a continuous or disperse phase of an emulsion including the one or more edible oils.
Water-soluble vitamins and/or minerals present in solid form in compositions of the invention preferably become at least temporarily suspended in, and coated with, the one or more edible oils. For example, in one embodiment of the invention, a solid form including a uniform mixture of the water-soluble B vitamins B6, B9 and B12 is coated with, and suspended within, an omega-3 oil. While not wishing to be bound by any theory, it is presently believed that, as a result of the vitamins and/or minerals, or particles thereof, being coated with one or more edible oils, or mixture thereof, compositions within the present invention may have an enhanced ability to transport water-soluble (or other) vitamins and/or minerals through the stomach of a mammal, which generally has a highly acid environment that is maintained by a secretion of hydrochloric acid, without being degraded, or substantially degraded, and, thus, permitting some or all of the water-soluble (or other) vitamins and/or minerals to be delivered to the intestinal tract of the mammal, where they can be absorbed and delivered to other parts of the mammal's body, such as the capillaries, the lymphatic system and the circulatory system, and produce one or more beneficial effects.
Compositions within the invention may be employed to provide, or enhance, nutritional, medical and/or other health benefits to mammals, whether in satisfactory health or having, or suffering from, one or more conditions, illnesses, diseases or disorders, including, but not limited to, depression, dementia, Alzheimer's disease, schizophrenia, rheumatoid arthritis, non-specific arthritis, osteoarthritis, osteoporosis, diabetes, neurological development, neurological degeneration, allergic disorders, immunologic disorders, cancer, pregnancy, lactation and disease states effected, or characterized, by elevated blood pressure, low HDL, arrhythmia, elevated levels of homocysteine, triglycerides and/or c-reactive protein and/or low levels of one or more of the components of the compositions of the invention.
Nutritional and Medical Benefits Provided by Edible Oils and Fatty Acids
Edible fats and oils generally provide nutritional, health and/or medical benefits to mammals. Fats are one of the three main classes of food, and are the most concentrated form of metabolic energy available to humans. Fats and oils are sources of essential fatty acids, an important dietary requirement, as well as other nutritious fatty acids.
Clinical studies have shown that certain edible oils containing DHA (an “omega-3” fatty acid) and other fatty acids can provide significant medical benefits to mammals, particularly to human beings. For example, both omega-3 and omega-6 fatty acids are associated with a lower risk of coronary heart disease. [Frank B. Hu, M. D. et al., “Types of Dietary Fat and Risk of Coronary Heart Disease: A Critical Review,” J Am Coll Nutr. 20(1): 5-19 (2001).]
Other publications that discuss the nutritional, health and/or medical benefits provided by edible oils include Elda Hauschildt, “Alpha-Linolenic Acid may help Prevent Heart Disease,” Am J Clin Nutr. Vol. 75, 221-227 (2002); Yvonne E. Finnegan et al., “Plant- and Marine-Derived n-3 Polyunsaturated Fatty Acids have Differential Effects on Fasting and Postprandial Blood Lipid Concentrations and on the Susceptibility of LDL to Oxidative Modification in Moderately Hyperlipidemic Subjects,” Am J Clin Nutr., Vol. 77, 783-795 (2003); Rozenn N. Lemaitre et al., “n-3 Polyunsaturated Fatty Acids, Fatal Ischemic Heart Disease, and Nonfatal Myocardial Infarction in Older Adults: the Cardiovascular Health Study,” Am J Clin Nutr., Vol. 77, 319-325 (2003); Dayong Wu et al., “Effect of Dietary Supplementation with Black Currant Seed Oil on the Immune Response of Healthy Elderly Subjects,” Am J Clin Nutr. Vol. 70(4), 536-543 (1999); Frank B. Hu et al., “Dietary Intake of α-Linolenic Acid and Risk of Fatal Ischemic Heart Disease Among Women,” Am J Clin Nutr. Vol. 69, 890-897 (1999); and EH Temme et al., “Comparison of the Effects of Diets Enriched in Lauric, Palmitic, or Oleic Acids on Serum Lipids and Lipoproteins in Healthy Women and Men,” Am J Clin Nutr., Vol 63, 897-903 (1996).
Fatty acids, such as “omega-3” fatty acids (also known as “n-3” fatty acids), “omega-6” fatty acids, “omega-9” fatty acids and essential fatty acids are generally present in high levels in various edible oils. “Omega-3 fatty acids” are the n-3 family of polyunsaturated fatty acids, and are called “n-3 fatty acids” because the first double bond occurs in the third carbon bond counting from the end or omega position of the fatty acid. Omega-3 fatty acids have many nutritional, health and/or medical benefits associated with them, and thus, can provide numerous beneficial effects to human beings and a wide variety of animals that ingest them, whether the consumers are healthy or have one or more conditions, illnesses, diseases or disorders. Although omega-3 fatty acids can be obtained from other sources, such as plant oils, fish have a unique ability to provide high levels of various specific fatty acids, such as the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Omega-3 fatty acids include, for example, docosahexaenoic acid (DHA), docosapentaenoic acid, alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), eicosatetraenoic acid, moroctic acid and heneicosapentenoic acid. Omega-3 fatty acids are precursors of eicosanoids (prostaglandins, thromboxanes and leukotrienes), which are signal substances (cell messengers) that can have a widely different effect upon biological activity. Many of these signal substances regulate physiological and immunological reactions.
Omega-3 fatty acids have been shown to be beneficial in the prevention of cardiovascular pathology, the reversal of atherosclerosis, the inhibition of tumor formation and the development and regulation of serum cholesterol. Prospective cohort studies and secondary prevention trials have provided strong evidence that an increased intake of n-fatty acids from fish or plant sources substantially lowers a risk of cardiovascular mortality. [Frank B. Hu, M. D. et al., “Types of Dietary Fat and Risk of Coronary Heart Disease: A Critical Review,” supra.] Other research suggests the therapeutic value of oils rich in omega-3 unsaturated fatty acids for disorders related to blood hyperviscosity, including the lowering of serum cholesterol and the suppression or reduction of plasma triglycerides, inflammatory autoimmune disorders, tumors and various other disorders. [D. F. Horrobin, “Clinical uses of Essential Fatty Acids,” Eden. Press, London, 1982.] The omega-3 fatty acids also suppress the production of the proinflammatory cytokines tumor necrosis factor (TNF), particularly TNF alpha, interleukin-1 (IL-1) and thromboxanes. The protective effects of n-3 fatty acids are likely a result of multiple mechanisms, including reducing triglyceride levels, reducing platelet aggregation and antiarrhythmic effects.
Omega-3 fatty acids are also essential for the normal development of an unborn baby's brain, especially during the third trimester, when the size of a baby's brain increases threefold. If a baby's mother fails to have a sufficient quantity of omega-3 fatty acids in her diet, the fetus will generally depend upon the mother's brain tissue and tissue storage of these omega-3 fatty acids. Lab tests have shown that new mothers have approximately one half of the normal blood levels of omega-3 fatty acids.
Linolenic acid, a polyunsaturated fatty acid having three double bonds, is a precursor to EPA and DHA, and is considered to be a dietary essential fatty acid. Because the body is not capable of synthesizing linolenic acid, it must be acquired from a dietary source, such as food or supplements.
DHA is an omega-3 long-chain fatty acid that is the primary structural fatty acid in the gray matter of the brain, and in the retina of the eye, and accumulates during the fetal period and the first year after birth. DHA is essential for normal visual and neurological (nervous system) development in infants, and for normal brain and eye function in adults. It is necessary for brain and eye development, growth and learning ability in children. [A. P. Simopoulos, “Omega-3 Fatty Acids in Health and Disease and in Growth and Development,” American Journal of Clinical Nutrition 54, No. 3, 438-463 (1991).]
The human body only synthesizes small quantities of DHA. As a result, it is generally necessary to obtain DHA from dietary sources. The primary source of DHA is fatty fish, such as mackerel, salmon, herring, sardines, black cod, anchovies and albacore tuna, and oils from the tissues of such fish.
DHA and EPA, which is associated with vascular regeneration, can alter eicosanoid and cytokine production, providing an improved immunocompetence (strengthening immune system activity) and a reduced inflammatory response to injury. The contributions of DHA and EPA in reducing the incidence of numerous inflammatory/circulatory disorders, cardiac problems and premature births, and in enhancing cognitive ability in children and mental well being, has been well documented.
ALA is an essential omega-3 fatty acid for humans. Adequate intake of ALA and long-chain omega-3 fatty acids is especially important for infants, young children and patients requiring parenteral and enteral nutrition. Experimental studies have suggested an antiarrhythmic effect of ALA, and beneficial effects of ALA on cardiovascular disease. [Frank B. Hu, M. D. et al., “Types of Dietary Fat and Risk of Coronary Heart Disease: A Critical Review,” supra.]
“Omega-6” fatty acids include gamma-linolenic acid (GLA), which is present in Black Current Seed Oil, linoleic acid, which is present in many vegetable oils, and arachidonic acid, which is present in many animal fats and in algae oil. GLA is an n 18:3 omega-6 polyunsaturated fatty acid that has been used in the amelioration of various diseases, such as eczema, rheumatoid arthritis and premenstrual syndrome, and that has been shown to improve the effectiveness of cancer chemotherapy. Arachidonic acid (ARA or AA) is an omega-6 polyunsaturated fatty acid that has been shown to play a role in early neurological and visual development, and is a precursor in the biosynthesis of some prostaglandins.
“Omega-9” fatty acids include, for example, oleic acid, which is present in sunflower oil, olive oil, avocados, canola oil and in many animal fats.
Marine oils (including “fish oils”) are oils that are obtained from aquatic lifeforms, either directly or indirectly, particularly from oily fish. Marine oils include, for example, herring oil, cod oil, anchovy oil, tuna oil, sardine oil, menhaden oil and algae oil. Fish that are employed to produce marine oils include, for example, farm-raised or wild, fresh-water or salt-water, fish and shellfish, such as herring, salmon, salmonoids, gadoids, shrimp, cod, carp, tilapia, perch, trout, sturgeon, krill, tuna, flat fish, anchovies, sardines, menhaden, shrimp, Mackerel, eels and seals. Marine oils may also be obtained from marine organisms, such as calanus (Calanus finmarchicus), a 3-4 mm copepod, algae and microalgae, for example, diatoms and dinoflagellates. Peru is currently the world's largest producer of fish oil.
Although omega-3 fatty acids can be obtained from other sources, such as plant oils, fish have a unique ability to provide high levels of the omega-3 fatty acids DHA and EPA. Fish and fish oils are also sources of the “omega-3” fatty acids docosapentaenoic acid, eicosatetraenoic acid, moroctic acid and heneicosapentenoic acid. Marine oils having a total “omega-3” fatty acid content of greater than about 20 weight percent include those derived from menhaden oil, herring, capelin, anchovy, cod liver, salmon oil, sardine oil and mixtures thereof. Oils containing omega-3 fatty acids, such as marine oils and DHA, are also referred to as “omega-3” oils or “n-3” oils.
A low rate of cardiovascular disease in populations that have a high intake of fish, such as Alaskan Native Americans, Greenland Eskimos and Japanese living in fishing villages, suggests that fish oil may be protective against artherosclerosis. [Frank B. Hu, M. D. et al., “Types of Dietary Fat and Risk of Coronary Heart Disease: A Critical Review,” supra.] Additionally, research into the blood chemistry of Eskimos, who consume large quantities of fish, showed low levels of low-density lipoproteins (LDL cholesterol) and high levels of high-density cholesterol (HDL cholesterol) in the blood despite a rich diet of fatty fish and seals. [Dyerberg et al., “Fatty Acid Composition of Plasma Lipids in Greenland Eskimos,” American Journal of Clinical Nutrition 28, 958-966 (1975).]
It is known that an oral administration of fish oil, which contains omega-3 fatty acids, has beneficial effects on cardiovascular and/or brain function, and has other health benefits. One article reports “a significant, graded, independent inverse association between base-line fish consumption and the 30-year risk of fatal myocardial infarction, particularly nonsudden death from myocardial infarction [that] accounted for the [observation of] lower rates of death from all coronary causes, all cardiovascular causes, and all causes in association with higher fish consumption . . . ” [Daviglus, M. L., et al., N Engl J Med 1997; 336(15): 1046-53.]
Another study found that, “dietary intake of omega-3 fatty acids, approximately 1.5 g/l for 2 years, modestly mitigated the course of human coronary atherosclerosis, as assessed by angiography. Fewer cardiovascular events were noted.” [Von Schacky, C., et al, Ann Intern Med. 1999; 130:554-62.] Yet, another study found that omega-3 fatty acids found in fish oil reduced the risk of sudden death in men without evidence of prior cardiovascular disease. [Albert, C. M., et al., N Engl J Med 2002; 346(15): 1113-18.]
There is growing evidence to suggest that fish oil may improve endothelial dysfunction, an early marker of atherosclerosis. In vitro studies have consistently shown that n-3 fatty acids decrease expression of adhesion molecules on the endothelium, and also decrease leukocyte/endothelium interactions. Further, clinical experimental studies have shown that n-3 fatty acid supplementation improves endothelial-dependent vasomotor function. [Frank B. Hu, M. D. et al., “Types of Dietary Fat and Risk of Coronary Heart Disease: A Critical Review,” supra.]
Various modified or unmodified fungi, such as filamentous fungi, also have an ability to produce lipids having high levels of fatty acids, such as GLA. Modified fungi have been employed to ferment DHA oil. Fungi can be isolated from soil and subsequently fermented using known techniques and conventional shake flasks or fermentation systems.
Many plant oils (including vegetable oils and plant seed oils), such as Evening Primrose oil, Black Currant seed oil, Borage oil, Borage seed oil, safflower oil, sunflower oil, peanut oil, olive oil, corn oil, soybean oil, coconut oil, palm oil, palm kernel oil, rapeseed oil, flaxseed (linseed) oil and cotton seed oil, contain high levels of fatty acids, such as GLA, as well as other fatty acids. For example, flaxseed oil, rapeseed oil and soybean oil contain a large quantity of ALA (about 20% in flaxseed oil and about 7% in unhydrogenated soybean oil). GLA is present in Evening Primrose oil, Black Currant seed oil and Borage seed oil, with the highest level of GLA being present in Borage seed oil. Safflower oil and sunflower oil are rich in linoleic acid. Olive oil contains a significant amount of oleic acid.
Numerous metabolic studies have shown strong cholesterol-lowering effects for vegetable oils that are rich in linoleic oil when substituted for dietary saturated fat. In addition, animal studies have suggested an anti-arrhythmic effect when sunflower oil (rich in linoleic acid) was consumed. [Frank B. Hu, M. D. et al., “Types of Dietary Fat and Risk of Coronary Heart Disease: A Critical Review,” supra.]
Plant oils can be extracted from plants or seeds using techniques that are known by those of skill in the art. For example, the highest quality Borage seed oil is generally extracted without hexane or the use of other chemical solvents. Rather, the Borage seed oil is “cold processed” using an expeller-press method of extraction, which simply squeezes the oil out from the seed without the use of heat.
With respect to neurological function, Morris, M. C., et al., Arch Neurol 2003: 60: 940-6, have shown that the omega-3 polyunsaturated fatty acids have “profound effects on membrane functions, leading to change in nerve conduction, neurotransmitter release, neurotransmitter reuptake, and postsynaptic transmitter effects. A large number of animal studies have demonstrated that dietary n-3 fatty acids increased learning acquisition and memory performance . . . ” See also, Horrocks, L. A. and Young, K. Y., Pharmacological Research 1999; 40(3): 211-25. (“Low levels of DHA are also associated with senile dementia (Alzheimer's disease) and schizophrenia,” and “Chronic alcohol intoxication depletes DHA from membranes of the neurons, leading to the common secondary depression in alcoholism.”)
Zanarini, M. C. and Frankenburg, F. R, Am J Psychiatry 2003; 160: 167-9, report results from a double-blind, placebo-controlled study that are “consistent with the findings of recent reports concerning omega-3-fatty acids as an effective adjunctive treatment for bipolar disorder and recurrent depression.”
Thus, there is substantial evidence that omega-3 fatty acids can beneficially affect a variety of diseases. See e.g., Conner, W. E., Am J Clin Nutr 2000; 71 (suppl): 171S-5S (omega-3 fatty acids “favorably affect atherosclerosis, coronary heart disease, inflammatory disease, and perhaps even behavioral disorders.”).
Nutritional and Medicinal Benefits Provided by
B-Vitamins and Other Water-Soluble Vitamins and Minerals
High levels of homocysteine (an amino acid) have been reported to be associated with cardiovascular diseases. Refsum, H. and Ueland, P. M., Annu Rev Medicine 1998; 49:31-62 report that “[a]n elevated level of total homocysteine (tHcy) in blood, denoted hyperhomocysteinemia, is emerging as a prevalent and strong risk factor for atherosclerotic vascular disease in the coronary, cerebral, and peripheral vessels, and for arterial and venous thromboembolism.” Similarly, Schnyder, G., et al., N Engl J Med 2001: 345(22): 1593-1600, report that the level of plasma homocysteine can be reduced significantly with a daily dose of folic acid in an amount of at least 500 micrograms, in combination with vitamin B6 (pyridoxine) and vitamin B 12 (cyanocobalamin, cobalamin, and/or reduced forms of cobalamin). “Roughly one half of US adults on a given day consume less than the newly lowered recommended dietary allowance for folate, and an estimated 88% consume less than the levels needed to produce low, stable homocysteine levels.” Morrison, H. I., et al. Serum Folate and Risk of Fatal Coronary Heart Disease JAMA 1996; 275(24): 1893-6.
Vitamin B9 (folic acid/folate) is thought to be crucial for proper brain function, and plays an important role in mental and emotional health. It aids in the production of DNA and RNA, the body's genetic material, and is especially important during periods of high growth, such as infancy, adolescence and pregnancy. Folic acid also works closely together with vitamin B12 to regulate the formation of red blood cells, and to help iron function properly in the body.
Vitamin B9 works closely with vitamins B6 and B12, as well as with the nutrients betaine and S-adenosylmethionine (SAM), to control blood levels of the amino acid homocysteine. Elevated levels of this substance appear to be linked to certain chronic conditions, such as heart disease and, possibly, depression and Alzheimer's disease. Some researchers have even speculated that there is a connection between high levels of this amino acid and cervical cancer, but the results of studies regarding this issue have been inconclusive.
Vitamin B 12 (cyanocobalamin, cobalamin, cobalamin bound to recombinant intrinsic factor (rhIF) and/or reduced forms of cobalamin) functions as a methyl donor and works with folic acid in the synthesis of DNA and red blood cells and is vitally important in maintaining the health of the insulation sheath (myelin sheath) that surrounds nerve cells. The classical vitamin B12 deficiency disease is pernicious anemia, a serious disease characterized by large, immature red blood cells. It is now clear, though, that a vitamin B12 deficiency can have serious consequences long before anemia is evident. Many elderly people are also deficient because their production of the intrinsic factor needed to absorb the vitamin from the small intestine declines rapidly with age.
Vitamin B12 plays an important role in maintaining a low blood concentration of homocysteine by participating in reactions that recycle homocysteine into methionine. In cases of a deficiency of vitamin B12, the conversion of homocysteine to methionine is inhibited. The resulting raised level of homocysteine has been estimated to be a greater risk factor and predicator for cardiovascular diseases than an increased level of cholesterol, high blood pressure, cigarette smoking, and elevated lipoproteins and hypertension. A B12 deficiency has also been suggested to be an independent risk factor for neural tube birth defects. Neural tube defects (NTDs) are a failure of closure of the neural tube, which includes the spinal cord and the brain, and is among the most devastating of all birth defects. A deficiency of vitamin B12 is thought to result in a lack of methionine, which is the sole precursor to the “universal methylator” (S-adenosylmethionine). S-adenosylmethionine participates in almost all methylation processes in the human body. A lack of S-adenosylmethionine slows the growth and/or closure of the neural tube and, thereby, increases the risk of NTDs. Lower plasma levels of vitamin B12 have also been associated with breast cancer. Vitamin B12, along with folate and vitamin B6, functions as a coenzyme in the building of components for DNA synthesis. Inadequate levels of vitamin B12 may cause misincorporation of uracil, normally found in RNA, into DNA, which may result in chromosome breaks and disruption of DNA repair. Additionally, a deficiency of vitamin B12 may cause aberrant DNA methylation, which has been observed in human tumors. Vitamin B12 deficiency is particularly associated with cognitive impairment and widespread pathology in the central nervous system in the elderly. In cells, vitamin B12 is converted to coenzymes, which influence brain function through the one carbon metabolism/methylation cycle. Vitamin B12 is required for the synthesis of methionine and S-adenosylmethionine, which the brain relies on to metabolize homocysteine. Furthermore, S-adenosylmethionine dependant reactions include the formation of neurotransmitters, phospholipids and myelin. Thus, vitamin B12 deficiency may cause nervous system dysfunction in the elderly. A severe and progressive consequence of a deficiency of vitamin B12 is the degeneration of the spinal cord. Classical symptoms include symmetrical parasthesias in the hands and feet leading to numbness, muscle weakness and paralysis.
Need for a Dosage Form Incorporating Both Fatty Acids and B-Vitamins
In view of the significant nutritional, medical and/or other health benefits provided by many edible oils, such as the omega-3 fatty acids DHA, EPA AND ALA, AND BY WATER-SOLUBLE vitamins and/or minerals, such as B-vitamins, it would be beneficial to provide oral dosage forms for an oral administration to mammals, or suppository dosage forms, that include one or more edible oils and one or more water-soluble vitamins and/or minerals, such as B-vitamins, that properly disintegrate, thereby allowing the edible oils and water-soluble vitamins and/or minerals to become bioavailable, that may permit the edible oils and water-soluble vitamins and/or minerals to be absorbed by the body without being substantially or fully degraded in the acidic environment of the stomach, and that may have a long shelf life under room temperature conditions.
Compositions within the present invention provide oral dosage forms for an oral administration to mammals, and suppository dosage forms, that preferably include one or more edible oils, one or more water-soluble vitamins and/or minerals, such as B-vitamins, one or more suspending agents and, optionally, one or more other components, such as antioxidants, emulsifiers or diluents, that properly disintegrate, thereby allowing the edible oils and water-soluble vitamins and/or minerals to become bioavailable, that may permit the edible oils and water-soluble vitamins and/or minerals to be absorbed by the body without being substantially or fully degraded in the acidic environment of the stomach, and that may have a long shelf life under room temperature conditions.
In view of the foregoing benefits, compositions within the present invention may be effective for improving cardiovascular function, lowering the incidence of myocardial infarction, improving cardiac arrhythmia problems and/or lowering elevated homocysteine levels which, in turn, may have a benefit of lowering the incidence of heart disease and/or depression.
2. Description of the Related Art
The Physicians' Desk Reference (49th Edition, 1995, and 54th Edition, 2000) describes a prenatal vitamin and mineral tablet marketed by Lederle Laboratories (Wayne, N.J.) under the trademark name Materna® (pages 1264 and 1534, respectively).
U.S. Pat. No. 5,494,678 discloses multi-vitamin and mineral supplements for incorporation into tablets, powders, granules, beads, lozenges, capsules and liquids, and administration to a pregnant woman during her first, second and third trimesters of pregnancy. The supplements contain specific regimens of a calcium compound, vitamin D, folic acid, vitamin B12, vitamin B6, and vitamin B1.
U.S. Pat. No. 5,571,441 discloses nutritional supplement compositions containing vitamins, minerals, central nervous system bracers, such as caffeine, and flavenols, that are coadministered in the form of a tablet or capsule, as a powder, or as a liquid form.
U.S. Pat. No. 5,869,084 discloses multi-vitamin and mineral supplements for administration to lactating, non-lactating (but not pregnant) and menopausal women in the form of tablets, powders, granules, beads, lozenges, capsules or liquids.
U.S. Pat. No. 5,906,833 discloses nutritional supplements that contain vitamins.